The South China Karst (SCK) represents a prototypical ecologically fragile region. Traditional vulnerability assessments, which focus primarily on natural ecosystems, fail to account for integrated Socio-Ecological Systems (SES). This gap underscores the need for an in-depth analysis of regional vulnerability to inform sustainable development strategies. In this study, we propose a susceptibility-adaptability-based vulnerability assessment framework, specifically designed for the core karst desertification control (KDC) zone in southern China. Using integrated metrics, geospatial analysis, and geographic detectors, we quantify vulnerability trends (2010-2020) and identify key drivers. Multi-scenario projections derived from ordered weighted averaging (OWA) guide policy recommendations. Key findings include: (1) System vulnerability declined steadily over the study period, with low-to-moderate risk zones increasing from 72.58% (2010) to 88.14% (2020). Elevated vulnerability persisted in northern and southern peripheries, attributed to anthropogenic pressures. (2) Social factors-notably demographic concentration and construction land expansion-exerted greater influence on vulnerability than ecological factors. Synergistic interactions among drivers amplified impacts (maximum q-value = 0.8655), emphasizing socio-economic determinants. (3) The sustainable development scenario (alpha = 0.8) could significantly reduce vulnerability, whereas the economy-priority scenario (alpha = 1.2) would expand high-risk areas. The study suggests that population aggregation and land development intensity should be prioritized for regulation, while enhancing the synergistic effects of landscape pattern optimization and ecological restoration. Multi-factor synergistic governance strategies should be adopted to achieve dynamic balance.